Working memory and response inhibition in patients with bipolar I disorder during euthymic period

Background: Several cognitive domains, including attention, memory, and executive functions are impaired in bipolar disorder. Objectives: This study aimed to investigate two executive functions (working memory and response inhibition) in patients with bipolar I disorder during remission of the symptoms. Patients and Methods: In this case-control design, 30 bipolar I patients (18 to 45 years old) were matched with 30 ones in the control group in terms of age, gender, and education. The patients were selected from Roozbeh Psychiatric Hospital (a hospital affiliated to Tehran University of Medical Sciences) from May to October 2013. They were evaluated and contrasted using working memory (Spatial Span and Spatial Working Memory (SSP and SWM)) and response inhibition (Stop Signal Task (SST)) tests. Results: We used independent t-tests for comparing and contrasting 2 groups on total and sub-scales scores of these 3 tests. In terms of SWM test there was a significant difference in between-group error between the two groups (P = 0.05); there was also a meaningful difference between the strategies used by two groups (P = 0.05). In SSP test, a significant difference appeared between averages of span length of the two groups. In the first and last item delays, there was also a clear difference, but the total error index was not noticeably different. In SST test, the direction error indicator in start-stop trials indicated a major difference, while in successful stops ratio, the case group had a lower ratio. In addition, reaction time to stop signs in bipolar group was meaningfully lower than the control group. Conclusion: In conclusion, even during remission phase, executive dysfunction is detectable at least in some areas in patients with bipolar disorder. © 2015, Mazandaran University of Medical Sciences

Reduction in ischemic brain injury following the administration of pentoxifylline after transient global ischemia/reperfusion in a rat model

Background: It is well known that the hippocampus, the CA1 Pyramidal cells in particular, is selectively vulnerable during global cerebral ischemia. Recently, it is observed that pentoxifylline has a neuroprotective effect. This study explored the pharmacological relationship between ischemiainduced cell death of the hippocampus and the efficacy of a vasodilator agent (pentoxifylline) in the prevention of delayed neuronal death. Methods: This experimental study was performed on 4 groups: control, ischemia, experimental (200mg/kg pentoxifylline injection one hour prior to and one hour following ischemia) and vehicle (normal saline). Transient global ischemia was induced by bilateral common carotid arteries occlusion. To investigate the apoptotic bodies and caspase-3 activities as a central role in the execution phase of apoptosis, the brains were prepared for the TUNEL technique. Results: Pentoxifylline administration limited apoptosis and caspase-3 activities in rats' hippocampi. Our data showed no significant difference between the number of apoptotic bodies in the CA1 region of the hippocampus in the control and pentoxifylline -treated groups (p= 0.994). The results of one- way ANOVA revealed that that ischemia significantly increased caspase-3 levels in the hippocampus (p< 0.05); however, the level of caspase-3 in pentoxifylline -treated rats was less than the ischemic group. Conclusion: These results suggest that the neuroprotective effect of pentoxifylline (200mg/kg) may be accompanied by a reduction in ischemic damage within the CA1 region of the hippocampus in rats subjected to transient global cerebral ischemia

Growth and development status in the first two years of uninfected children born from HIV positive mothers

Recently prevention of HIV transmission from mother to child by antiretroviral regimens has resulted in growing the numbers of HIV exposed but uninfected children (HIV-EU). The aim of present study was evaluation of growth and neurodevelopment status among less than 2-year-old HIV exposed uninfected children. A cohort study was carried out at Vali-e-Asr Hospital (Tehran-Iran). Thirty-nine HIV-EU neonates were recruited (2014 to 2016). Neonates and infants with concern to growth and neurodevelopment status were evaluated at 6, 12, 18, and 24 months by an expert physician. Neurodevelopment assessment was based on WHO Milestones Chart and Age and Stage Questionnaire. Of all children, 22 were male, and 17 were female. Regarding growth indices, although mean birth weight in half of the neonates was lower than normal population; no postnatal descending trend was observed in their growth chart. No significant differences were found between two groups' height and head circumference. Among the neurodevelopmental parameters measured, in 6th months of life, 2 cases had abnormality in the gross motor while at 12 months, 6 cases had delay in language, social problem, and motor disorders. At 18 and 24 months, 7 infants showed developmental problems of which 71.4 of their mothers were younger than others (age&lt;25 years, P=0.009). Prevalence of neurodevelopmental disorders including delay in language, motor, and social domains was common among HIV-EU children. As several environmental factors may involve the etiology of neurodevelopmental disorders, nearly-full postnatal control and prevention seem necessary. © 2018 Tehran University of Medical Sciences. All rights reserved

Growth and development status in the first two years of uninfected children born from HIV positive mothers

Recently prevention of HIV transmission from mother to child by antiretroviral regimens has resulted in growing the numbers of HIV exposed but uninfected children (HIV-EU). The aim of present study was evaluation of growth and neurodevelopment status among less than 2-year-old HIV exposed uninfected children. A cohort study was carried out at Vali-e-Asr Hospital (Tehran-Iran). Thirty-nine HIV-EU neonates were recruited (2014 to 2016). Neonates and infants with concern to growth and neurodevelopment status were evaluated at 6, 12, 18, and 24 months by an expert physician. Neurodevelopment assessment was based on WHO Milestones Chart and Age and Stage Questionnaire. Of all children, 22 were male, and 17 were female. Regarding growth indices, although mean birth weight in half of the neonates was lower than normal population; no postnatal descending trend was observed in their growth chart. No significant differences were found between two groups' height and head circumference. Among the neurodevelopmental parameters measured, in 6th months of life, 2 cases had abnormality in the gross motor while at 12 months, 6 cases had delay in language, social problem, and motor disorders. At 18 and 24 months, 7 infants showed developmental problems of which 71.4 of their mothers were younger than others (age&lt;25 years, P=0.009). Prevalence of neurodevelopmental disorders including delay in language, motor, and social domains was common among HIV-EU children. As several environmental factors may involve the etiology of neurodevelopmental disorders, nearly-full postnatal control and prevention seem necessary. © 2018 Tehran University of Medical Sciences. All rights reserved

Comparison of dietary micronutrient intake in PCOS patients with and without metabolic syndrome

Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. It is one of the risk factors of metabolic syndrome (MetS). These two syndromes have an inflammatory etiologic foundation along with oxidative stress. The present study aimed to compare the dietary intake of antioxidant micronutrients in PCOS women with and without MetS. Materials and methods: Overall, 42 participants eligible for this nested case control study were selected by the convenience sampling method. The case group included 14 PCOS patients with MetS and the control group included 28 PCOS patients without MetS. The dietary intake assessment of selenium, chromium, zinc, carotenoids, vitamin D and vitamin E was carried out by a 147-item Food Frequency Questionnaire (FFQ). PCOS and MetS were diagnosed using the Rotterdam criteria and NCEP ATP III, respectively. Statistical analysis was performed using SPSS16 software, T-test and Mann Whitney. Significant P-value was considered 0.05. Results: Dietary intake of antioxidant micronutrients (selenium, zinc, chromium, carotenoids and vitamin E) was significantly lower in the PCOS women with MetS than in the control group (P < 0.05). Conclusion: Since the PCOS patients without MetS had more intake of the aforementioned micronutrients than those with MetS, it is assumed that the dietary intake of these nutrients could probably have a protective effect on MetS. © 2021, The Author(s)

Quantitative analysis of particles, genomes and infectious particles in supernatants of haemorrhagic fever virus cell cultures

Information on the replication of viral haemorrhagic fever viruses is not readily available and has never been analysed in a comparative approach. Here, we compared the cell culture growth characteristics of haemorrhagic fever viruses (HFV), of the Arenaviridae, Filoviridae, Bunyaviridae, and Flavivridae virus families by performing quantitative analysis of cell culture supernatants by (i) electron microscopy for the quantification of virus particles, (ii) quantitative real time PCR for the quantification of genomes, and (iii) determination of focus forming units by coating fluorescent antibodies to infected cell monolayers for the quantification of virus infectivity

An efficient, chemically-defined semisynthetic lipid-adjuvanted nanoparticulate vaccine development system

A novel vaccine development platform that enables the site-specific conjugation of synthetic lipid adjuvants to recombinant proteins was produced. This technology facilitates the simple and efficient production of homogeneous, chemically-defined, semisynthetic lipoprotein vaccines. Using a polytope 'string-of-beads' approach, a synthetic gene incorporating seven Streptococcus pyogenes M protein strain-specific antigens, and a conserved M protein antigen (J14) was produced, expressed, and attached to a lipoamino acid based adjuvant (lipid core peptide; LCP). Nanoparticles (40 nm diameter) of an optimal size for stimulating antibody-mediated immunity were formed upon the addition of these lipoproteins to aqueous buffer (PBS). Systemic antigen-specific IgG antibodies were raised against all eight antigens in C57BL/6 J mice, without the need to formulate with additional adjuvant. These antibodies bound cell surface M proteins of S. pyogenes strains represented within the polytope sequence, with higher antibody levels observed where a dendritic cell targeting peptide (DCpep) was incorporated within the LCP adjuvant. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved

Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD.</p> <p>Methods</p> <p>Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA.</p> <p>Results</p> <p>Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.</p> <p>Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.</p> <p>In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A.</p> <p>Conclusions</p> <p>Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis.</p

Macrophage-Specific Chemokines Induced via Innate Immunity by Amino Acid Copolymers and Their Role in EAE

The random amino acid copolymer poly(Y,E,A,K)n (Copaxone®) is widely used in multiple sclerosis treatment and a second generation copolymer poly(Y,F,A,K)n with enhanced efficacy in experimental autoimmune encephalomyelitis in mice has been described. A major mechanism through which copolymers function to ameliorate disease is the generation of immunosuppressive IL-10-secreting regulatory T cells entering the CNS. In addition, the antigen presenting cell to which these copolymers bind through MHC Class II proteins may have an important role. Here, both CCL22 (a Th2 cell chemoattractant) in large amounts and CXCL13 in much smaller amounts are shown to be secreted after administration of YFAK to mice and to a smaller extent by YEAK parallel to their serum concentrations. Moreover, bone marrow-derived macrophages secrete CCL22 in vitro in response to YFAK and to higher concentrations of YEAK. Strikingly, these chemokines are also secreted into serum of MHC Class II −/− mice, indicating that an innate immune receptor on these cells also has an important role. Thus, both the innate and the adaptive immune systems are involved in the mechanism of EAE amelioration by YFAK. The enhanced ability of YFAK to stimulate the innate immune system may account for its enhanced efficacy in EAE treatment

Dose-Dependent Immunomodulation of Human Dendritic Cells by the Probiotic Lactobacillus rhamnosus Lcr35

The response of the immune system to probiotics remains controversial. Some strains modulate the cytokine production of dendritic cells (DCs) in vitro and induce a regulatory response, while others induce conversely a pro-inflammatory response. These strain-dependent effects are thought to be linked to specific interactions between bacteria and pattern recognition receptors. We investigated the effects of a well characterized probiotic strain, Lactobacillus rhamnosus Lcr35, on human monocyte-derived immature DCs, using a wide range of bacterial concentrations (multiplicity of infection, MOI, from 0.01 to 100). DNA microarray and qRT-PCR analysis showed that the probiotic induced a large-scale change in gene expression (nearly 1,700 modulated genes, with 3-fold changes), but only with high doses (MOI, 100). The upregulated genes were mainly involved in immune response and identified a molecular signature of inflammation according to the model of Torri. Flow cytometry analysis also revealed a dose-dependent maturation of the DC membrane phenotype, until DCs reached a semi-mature state, with an upregulation of the membrane expression of CD86, CD83, HLA-DR and TLR4, associated with a down-regulation of DC-SIGN, MR and CD14. Measurement of the DC-secreted cytokines showed that Lcr35 induced a strong dose-dependent increase of the pro-Th1/Th17 cytokine levels (TNFα, IL-1β, IL-12p70, IL-12p40 and IL-23), but only a low increase in IL-10 concentration. The probiotic L. rhamnosus Lcr35 therefore induce a dose-dependent immunomodulation of human DCs leading, at high doses, to the semi-maturation of the cells and to a strong pro-inflammatory effect. These results contribute to a fuller understanding of the mechanism of action of this probiotic, and thus of its potential clinical indications in the treatment of either infectious or IgE-dependent allergic diseases